Project highlights: HTS screening and medicinal chemistry optimization lead to a first in class drug like small molecule inhibitor of APE1. The probe molecule ML199 has been delivered to multiple collaborators to study in cancer therapy. Currently pursuing a large screen to identify potent compounds with improved PK properties. During this period, the NCGC has fostered and maintained over 180 active collaborations with both NIH and extramural investigators, facilitating drug discovery efforts across the entire spectrum of human disease. These efforts have led to over 100 high-throughput screens and nearly 60 medicinal chemistry campaigns, providing our collaborators and the general research community a wealth of publications and promising small molecule leads. In addition, the NCGC has undertaken a number of informatic challenges to make better use of existing drug and disease target information and provide the general public with easily accessible resources, further catalyzing the development of new therapies for human disease.